We have shown that amplitude histograms of spontaneous miniature end-plate potentials (MEPPs) of mouse and frog neuromuscular junctions are multimodal and that the various peaks are integral multiples of the first peak. The number of peaks depends on the MEPP frequency which can be altered by temperature, calcium, botulinum toxin, and colchicine. We have proposed that the smallest peak of MEPP amplitude histograms represents the quantum of spontaneous release and that larger MEPPs result from the synchronous release of the sub-MEPPs. Normal and myasthenic human muscle will be examined for the presence of sub-MEPPs. We have also found that small unitary evoked end-plate potentials (EPPs) the size of sub-MEPPs are sometimes evoked during nerve stimulation (EPPs reduced to unitary responses with Co ions). Some unitary evoked EPP histograms appeared to be multimodal. A major goal for the current year is to determine if the unitary evoked potential is also composed of the same subunits as those which generate MEPPs. We will also determine the effects of colchicine, Ca ions, temperature challenges, botulinum toxin and polarizing electrical currents on evoked transmitter release.